Authors Karna T. Sura, Leslie Kohman, Danning Huang, Silviu V. Pasniciuc Published June 28, 2022 DOI: 10.7759/cureus.26406 Citations Sura K T, Kohman L, Huang D, et al. (June 28, 2022)…
Breast cancer is the most common malignancy in women worldwide. Sixty-five percent of breast cancers are estrogen and/or progesterone receptor positive. Estrogen receptor expression is a prognostic and predictive biomarker of response to endocrine therapy, which consists of the selective estrogen receptor modulator tamoxifen, aromatase inhibitors, and the selective estrogen receptor degrader fulvestrant. Cannabidiol is a phy- tocannabinoid that is emerging as a potential therapeutic agent. The aim of this study was to investigate the effect of cannabidiol on estrogen receptor-positive and estrogen receptor-negative representative breast cancer cell lines in combination with standard therapeutic agents used in clinical practice.
Cancer is a complex family of diseases affecting millions of people worldwide. Gliomas are primary brain tumors that account for ~80% of all malignant brain tumors. Glioblastoma multiforme (GBM) is the most common, invasive, and lethal subtype of glioma. Therapy resistance and intra-GBM tumoral heterogeneity are promoted by subpopulations of glioma stem cells (GSCs). Cannabis sativa produces hundreds of secondary metabolites, such as flavonoids, terpenes, and phytocannabinoids. Around 160 phytocannabinoids have been identified in C. sativa. Cannabis is commonly used to treat various medical conditions, and it is used in the palliative care of cancer patients. The anti-cancer properties of cannabis compounds include cytotoxic, anti-proliferative, and anti-migratory activities on cancer cells and cancer stem cells. The endocannabinoids system is widely distributed in the body, and its dysregulation is associated with different diseases, including various types of cancer. Anti-cancer activities of phytocannabinoids are mediated in glioma cells, at least partially, by the endocannabinoid receptors, triggering various cellular signaling pathways, including the endoplasmic reticulum (ER) stress pathway. Specific combinations of multiple phytocannabinoids act synergistically against cancer cells and may trigger different anti-cancer signaling pathways. Yet, due to scarcity of clinical trials, there remains no solid basis for the anti-cancer therapeutic potential of cannabis compounds.
High-grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB1 and CB2 receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti-tumoral effects by modulating key intracellular signaling path- ways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell-like properties of cancer cells, thereby affecting the complex tumor microenvi- ronment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context-dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid-based anti-tumoral therapies, as well as the preliminary clinical testing that is currently underway.
Cannabidiol (CBD) is one of the main constituents of the plant Cannabis sativa.
Surveys suggest that medicinal cannabis is popular amongst people diagnosed with cancer. CBD
is one of the key constituents of cannabis, and does not have the potentially intoxicating effects
that tetrahydrocannabinol (THC), the other key phytocannabinoid has. Research indicates the CBD
may have potential for the treatment of cancer, including the symptoms and signs associated with
cancer and its treatment. Preclinical research suggests CBD may address many of the pathways
involved in the pathogenesis of cancers. Preclinical and clinical research also suggests some evidence
of efficacy, alone or in some cases in conjunction with tetrahydrocannabinol (THC, the other key
phytocannabinoid in cannabis), in treating cancer-associated pain, anxiety and depression, sleep
problems, nausea and vomiting, and oral mucositis that are associated with cancer and/or its
treatment. Studies also suggest that CBD may enhance orthodox treatments with chemotherapeutic
agents and radiation therapy and protect against neural and organ damage. CBD shows promise as
part of an integrative approach to the management of cancer.
We previously reported that both cannabidiol (CBD) and low‑dose naltrexone (LDN) exhibit complex effects on G‑protein coupled receptors, which can impact the expression and function of other members of this superfamily. These receptors feed into and interact with central signalling cascades that determine the ease by which cells engage in apoptosis, and can be used as a way to prime cancer cells to other treatments. The present study was designed to investigate the effect of combining these two agents on cancer cell lines in vitro and in a mouse model, and focused on how the sequence of administration may affect the overall action. The results showed both agents had minimal effect on cell numbers when used simultaneously; however, the combination of LDN and CBD, delivered in this specific sequence, significantly reduced the number of cells, and was superior to the regimen where the order of the agents was reversed. For example, there was a 35% reduction in cell numbers when using LDN before CBD compared to a 22% reduction when using CBD before LDN. The two agents also sensitised cells to chemotherapy as significant decreases in cell viability were observed when they were used before chemotherapy. In mouse models, the use of both agents enhanced the effect of gemcitabine, and crucially, their use resulted in no significant toxicity in the mice, which actually gained more weight compared to those without this pre‑treatment (+6.5 vs. 0%). Overall, the results highlight the importance of drug sequence when using these drugs. There is also a need to translate these observations into standard chemotherapy regimens, especially for common tumour types where treatment is often not completed due to toxicities.
Currently, there is no effective therapy against lung cancer due to the development of resistance. Resistance contributes to disease progression, recurrence, and mortality. The presence of so-called cancer stem cells could explain the ineffectiveness of conventional treatment, and the development of successful cancer treatment depends on the targeting also of cancer stem cells. Cannabidiol (CBD) is a cannabinoid with anti-tumor properties. However, the effects on cancer stem cells are not well understood. The effects of CBD were evaluated in spheres enriched in lung cancer stem cells and adherent lung cancer cells. We found that CBD decreased viability and induced cell death in both cell populations.
Conventional lung cancer treatments include surgery, chemotherapy and radiotherapy; however, these treatments are often poorly tolerated by patients. Cannabinoids have been studied for use as a primary cancer treatment. Cannabinoids, which are chemically similar to our own body’s endocannabinoids, can interact with signalling pathways to control the fate of cells, including cancer cells. We present a patient who declined conventional lung cancer treatment. Without the knowledge of her clinicians, she chose to self-administer ‘cannabidiol (CBD) oil’ orally 2–3 times daily. Serial imaging shows that her cancer reduced in size progressively from 41 mm to 10 mm over a period of 2.5 years. Previous studies have failed to agree on the usefulness of cannabinoids as a cancer treatment. This case appears to demonstrate a possible benefit of ‘CBD oil’ intake that may have resulted in the observed tumour regression. The use of cannabinoids as a potential cancer treatment justifies further research.
The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable.
Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties.
Medical marijuana (MM) use is common among cancer patients, but relatively little is known about the usage patterns and efficacy of MM used by gynecologic cancer patients.
The endocannabinoid system (ECS), a conserved physiological system emerged as a novel pharmacological target for its significant role and potential therapeutic benefits ranging from neurological diseases to cancer. Among both, CB1 and CB2R types, CB2R have received attention for its pharmacological effects as antioxidant, anti-inflammatory, immunomodulatory and antiapoptotic that can be achieved without causing psychotropic adverse effects through CB1R.